Spending Money to Save Money - Cardiovascular Disease Management

There are a few avenues in health care where it is clear that spending money will save money. To assess accurately the value-for-money opportunity, one needs knowledge of at least 3 critical factors: (1) the probability associated with the risk factor and the outcome, (2) relative costs of alternate interventions to modify the risk factor, and (3) methods to improve target population adherence to the intervention. Research conducted among populations in 52 countries found that 9 of 10 heart attacks can be predicted on the basis of 9 risk factors, which are the same all over the world irrespective of ethnic group or gender. Two thirds of the risk of heart attack is accounted for by 2 factors—an abnormal ratio of apolipoprotein A to apolipoprotein B (a more sensitive measure than the ratio of high-density to low-density lipoprotein) and smoking. Smoking 6 to 10 cigarettes a day doubles the risk of heart attack, and the research found a direct proportional relationship between the number of cigarettes per day and heart attack risk. INTERHEART is the first study that matched first heart attack patients (n = 15,152) with controls (without heart disease, n=14,820), and the monitoring period was 10 years. The need for the INTERHEART research was driven by the realization that the knowledge of the relative importance of risk factors and cardiovascular disease had been derived from populations in the developed countries that account for only about 20% of the global burden of cardiovascular disease. The results from INTERHEART showed that diabetes and a history of hypertension also had high odds ratios and, along with abdominal obesity, psychosocial factors, consumption of fruits, vegetables, alcohol, and regular physical activity accounted for the remaining 25% of identifiable risk for heart attack. Hypertension is an expensive disease in morbidity, mortality, and economic cost. Estimates from the American Heart Association put hypertension-related morbidity and mortality at more than $34.4 billion in health care expenditures and an additional $12.8 billion in lost productivity in 2002. The results of the monumental ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) helped shape the value-for-money equation that exists in cardiovascular disease management. ALLHAT showed that low-cost, generic diuretics (chlorthalidone) can treat hypertension and coronary heart disease as effectively as higher-cost angiotensin-converting enzyme inhibitors ([ACEIs] lisinopril) or calcium channel blockers (amlodipine). The results of the OPTIMAAL (Optimal Trial in Myocardial Infarction with Angiotensin II Antagonists Losartan) study, another randomized control trial (RCT), showed that generic, low-cost captopril was more effective than high-cost, brand-only losartan (Cozaar) in preventing cardiac death. Specifically, the OPTIMAAL trial found a similar overall death rate, 18.2% (499 deaths) for losartan versus 16.4% (447 deaths) for captopril (P = 0.07) but a higher death rate due to cardiac causes, 15.3% (420) for losartan versus 13.3% (363) for the captopril group (P=0.032). In the well-controlled OPTIMAAL clinical trial, losartan was dosed initially at 12.5 mg per day and titrated up to a maximum dose of 50 mg per day, beginning within 10 days of the myocardial infarction (MI). Captopril was dosed initially at 6.25 mg per day, titrated to 12.5 mg thrice daily, up to a maximum dose of 50 mg thrice daily. The combination of data from 42 long-term RCTs, published through December 2002 and involving a total of 192,478 patients, showed that low-dose diuretics were superior to all alternative pharmacotherapy in reducing the risk of cardiovascular morbidity and mortality. This meta-analysis found that low-dose diuretics were superior to placebo for all outcomes: coronary heart disease; relative risk [RR] 0.79; 95% confidence interval [CI], 0.69-0.92), congestive heart failure ([CHF]; RR 0.51; 95% CI, 0.42-0.62); stroke (RR 0.71; 95% CI, 0.63-0.81), cardiovascular disease events (RR 0.76; 95% CI, 0.69-0.83), cardiovascular disease mortality (RR 0.81; 95% CI, 0.73-0.92), and total mortality (RR 0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies—beta-blockers, ACEIs, calcium channel blockers (CCBs), alpha-blockers, and angiotensin receptor blockers (ARBs)—was significantly better than low-dose diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated with reduced risks of cardiovascular disease events (RR 0.94; 95% CI, 0.89-1.00) and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACEIs, low-dose diuretics were associated with reduced risks of CHF (RR 0.88; 95% CI, 0.80-0.96), cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR 0.86; 0.77-0.97). Compared with beta-blockers, low-dose diuretics were associated with a reduced risk of cardiovascular disease events (RR 0.89; 95% CI, 0.80-0.98). Compared with alpha-blockers, low-dose diuretics were associated with reduced risks of CHF (RR 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events (RR 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between comparison treatments. The authors concluded that (a) low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality, (b) clinical practice and treatment guidelines should reflect this evidence, and (c) and future trials should use low-dose diuretics as the standard for clinically useful comparisons. The combined results of the ALLHAT and OPTIMAAL RCTs and the meta-analysis from 42 long-term RCTs provide convincing evidence that drug therapy to reduce blood pressure and reduce the risk of cardiac death can be relatively inexpensive and accomplished with the use of generic drugs. The results of these studies are important weapons for managed care clinicians and administrators who are charged with maximizing favorable clinical outcomes at lower cost. However, while knowledge is fundamental to achievement of quality improvement, it can be an uphill battle for managed care clinicians. Analysis of a population sample with essential

The combined results of the ALLHAT and OPTIMAAL RCTs and the meta-analysis from 42 long-term RCTs provide convincing evidence that drug therapy to reduce blood pressure and reduce the risk of cardiac death can be relatively inexpensive and accomplished with the use of generic drugs. The results of these studies are important weapons for managed care clinicians and administrators who are charged with maximizing favorable clinical outcomes at lower cost. However, while knowledge is fundamental to achievement of quality improvement, it can be an uphill battle for managed care clinicians. Analysis of a population sample with essential www.amcp.org Vol. 10 hypertension found health maintenance organization (HMO) members compared with persons with fee-for-service health insurance or no health insurance were more likely to receive ACEIs and CCBs than diuretics and beta-blockers. 7 Drug product promotion may be a factor in this difference. Drug product promotion reached a new level in mid-2004 when the manufacturer of an ARB and a combination product (amlodipine and benazepril) launched a campaign, "Take Action for Health BP," that included a money-back guarantee if a patient does not reach blood pressure control at the maximum approved dose of either drug. 8 So, we have a modifiable risk factor (hypertension) that is associated with heart attack and other adverse cardiovascular outcomes and evidence that low-cost pharmacotherapy can lower the risk of adverse cardiovascular outcomes to the same extent as higher-cost pharmacotherapy. So what is missing?
Many lament the shortfall in blood pressure control at a population level. In the Hypertension Initiative of South Carolina, involving 63 practice sites and 201 primary care physicians, only 49% of 35,940 enrollees in the intervention had blood pressure controlled to 140/90 mm Hg or less at the last recorded visit. 9 Andrade et al. found that 11% of 681 members of an HMO with a diagnosis of hypertension were at target blood pressure for all outpatient visits, 38% were at target blood pressure for at least one half of their outpatients visits, and 3% were not at target blood pressure for any visit. 10 In this issue of the Journal of Managed Care Pharmacy, Jackson, Frech, Ronen, et al. join a long list of authors that decry the "deficit" in blood pressure control, citing a 28% incidence of blood pressure control in patients with hypertension and heart failure among 12 managed care organizations (MCOs). 11 These authors highlight the missed opportunity in managed care. But just how large is the magnitude of this missed opportunity and what can be done about it?
As noted below, the Congressional Budget Office concluded, in a comprehensive study, that disease management programs may have the potential to improve quality of care but have not been shown to have a favorable return on investment, while others have found that nurse case management of patients with poorly controlled diabetes had no effect on physiologic outcomes. Goff et al. found, in a randomized, practice-based trial, that a quality improvement project intended to enhance the use of lipid-lowering therapy, beta-blocker therapy, and ACE-inhibitor therapies, had no effect on quality of care in a managed care setting. 12 Eight years of data collected and reported by the National Committee for Quality Assurance (NCQA) suggest that the magnitude of the missed opportunity in blood pressure control is time relative. In The State of Health Care Quality 2004 report, NCQA found that key measures of clinical quality had improved each year for the past 5 years. 13  Editorialists Campbell and Murchie writing in the British Medical Journal found that the rule of halves (e.g., one half of treated hypertensive patients reach target goal) is now the rule of thirds since the target blood pressure goals are lower. 14 So, should clinicians and health plan administrators beat themselves up for failure? Campbell and Murchie suggest that target goals in clinical guidelines are arbitrary, and we might take a different perspective-that any reduction in blood pressure is helpful in hypertensives. The release of 2 new hypertension guidelines in the United Kingdom this year, from the National Institute for Clinical Excellence (NICE) 15 and from the British Hypertension Society (BHS IV), 16 were expected to receive a cool reception from primary care clinicians due, in smaller part, to the differences in the recommendations and, in larger part, to the targets themselves. And, at a hefty 261 pages, the NICE guideline for treating hypertension is not likely to be read by many clinicians.
Where is the evidence that a systolic pressure of 140 mm Hg is therapeutic failure but 139 mm Hg is therapeutic success? It is a fact that current blood pressure targets are unachievable for most patients. Most patients fail to achieve systolic blood pressures below 140 mm Hg even in clinical trials with prescribing dictated by study protocols for willing patients who are enrolled in the trials. 17 For persons older than 60 years or those with diabetes, the proportions that do not reach target systolic blood pressure goal are even larger. 18 There is clearly room for improvement in the proportion of persons with hypertension who are being treated and in the amount of blood pressure reduction in some persons who are receiving treatment for hypertension. However, the significance of the shortfall in the latter category is less clear.
A careful reader might also quibble with the call by Jackson, Frech, Ronen, et al. for greater use of ACEIs and ARBs in patients with hypertension and heart failure, particularly since their study did not include assessment of severity of heart failure, and we do not know what proportion of patients had systolic heart failure, diastolic heart failure, or both. Clinical trials such as Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) show that

Editorial Subjects-In This Issue and In Previous Issues
heart failure type and severity are important factors in determining the outcomes of treatment. 19 There is also a lack of evidence that ARBs are interchangeable with ACEIs in certain subgroups of patients, and the Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult from the American College of Cardiology/American Heart Association Task Force specify the use of ACEIs (but not ARBs) in patients with heart failure. 20 A systematic review of the results of published and unpublished RCTs of at least 6 months duration found strong evidence that ARBs are beneficial for renal outcomes, with about a 22% reduction in risk of end-stage renal disease and doubling of serum creatinine concentration, around a 51% reduction in progression rates from microalbuminuria to macroalbuminuria, and about a 42% increase in regression from microalbuminuria to normoalbuminuria. 21 However, while ACEIs significantly reduced all-cause mortality (RR 0.79; 95% CI, 0.63 to 0.99) compared with placebo, ARBs did not reduce all cause mortality (RR 0.99, 95% CI, 0.85 to 1.17).

ss David and Goliath-Employer Takes on Health Care Cost Management
Among the hand-wringing about escalating costs for health care payers are some nuggets of information about the source of the problem, if one looks hard enough. Employers sometimes receive notoriety for putting health care costs into perspective, such as the revelation that health care liabilities for General Motors exceed $60 billion in 2004 and that health care costs add $1,400 to each automobile produced by GM. 22 In 2004, GM estimated that the new Medicare legislation would do little to trim its enormous financial liability for the current and future costs of its retirees.
These sorts of stories give us perspective and, for that, are invaluable. But, in the end, these stories do not provide proscriptive advice about what to do about the problem. Hence, more hand-wringing ensues, perhaps with vague promises of salvation from disease management. In a recent review of the literature on cardiovascular disease management interventions conducted in managed care organizations, Ara concluded that there is a lack of agreement on the appropriate clinical and economic outcomes to evaluate whether these interventions are effective. 23 In perhaps the most comprehensive and unbiased analysis of the disease management literature, the Congressional Budget Office (CBO) concluded, in a report dated October 13, 2004, that the evidence of cost savings from disease management programs is "quite limited" and that the methodological limitations of the studies of outcomes from disease management programs makes the results questionable. 24 The CBO report evaluated the entire literature on disease management programs and zeroed in specifically on congestive heart failure, coronary artery disease, and diabetes. Relying in large part on rigorous review of the literature by Ohman et al. 25 and others, the CBO concluded that there is some basis for suggesting that disease management may improve the quality of care but insufficient evidence to show that disease management offers an economic benefit and a favorable financial return on investment. Others have found that efforts to coordinate care in disease management of patients with poorly controlled diabetes did not improve physiologic outcomes. 26 The story of one employer who adopted an aggressive, hands-on campaign to reduce the increase in health care spending is worthy of attention by others who might consider self-management of health care costs. Pitney Bowes, Inc. (Stamford, CT) apparently identified health care costs as a manageable expense in 2000 and subsequently deployed an arsenal of good ideas in an attempt to slow the rise in health care costs. In addition to its 8 state-of-the-art medical clinics for its workers and their families, the company operates its own "Health Care University," where employees can earn credits toward lower health premium contributions by completing courses in subjects such as how to use health care services more efficiently. The company hired a physician medical director and has a 7-member health strategy team and analysts to determine the sources of the escalating costs. 27 The outcomes of these cost-management efforts are worth examining in greater detail. Pitney Bowes found in 2003, for example, that the average length of hospital stay-3.7 daysdid not change compared with 2002. When combined with the flat rate of hospital admissions per 1,000 employees, it was clear that hospital utilization had not changed. So why did hospital spending increase by nearly 10%? Those who work in managed care know the answer well-price increases. Pitney Bowes found that hospital prices had increased by 9% per visit, to an average $10,600, and the average cost per inpatient day increased by 17%. Its investigation was more precise: hospital costs in California were $20,500 per admission, twice what it paid elsewhere.
Armed with this information, the company found that it had little influence. Hospital corporations were powerful in California. Examination of medical claims experience was similarly discouraging. Claims data for its 46,000 health plan members showed that entrepreneurial physicians were prescribing more magnetic resonance imaging (MRI) and computed tomography (CT) scans, delivered at their owned imaging centers. For prescription drugs, which accounted for 19.5% of total medical costs for Pitney Bowes in 2003, spending was up 12% despite cost-management efforts. Spending for the proton pump inhibitor (PPI) esomeprazole (Nexium) pushed the drug to rank number 3 in drug expenditures. The over-the-counter (OTC) therapeutic equivalent, OTC omeprazole, is available at less than $20 per month of therapy compared with more than $120 for esomeprazole. 28 Effective marketing trumps employer costmanagement efforts. The executives of Pitney Bowes appear to have concluded from their collective cost-management efforts that member copays are perhaps useful tools but are not sufficient to effect successful cost management of health care expenditures, and the company will continue to build its own medical clinics and pursue other methods to influence provider behavior. Others have found that intelligent execution of tried-and-true managed care principles can improve cost outcomes. For example, Harris et al. showed that adding coverage of OTC omeprazole to a state employee drug benefit plan with 129,500 members could save the state about 50% on spending on PPIs, or about $4 million in one year. 29 These savings were realized after accounting for the average 17% savings per PPI prescription for plan beneficiaries (and 90% copayment savings per OTC omeprazole prescription) and an average 119% higher dispensing fee for pharmacies. 30